In chemical reaction, if it becomes possible to separate easily the aimed product from catalyst, additives for reaction or by-products, not only the numbers of necessary operations for separation can be reduced largely, but also the generation of wastes harmful to the environment can be effectively reduced by decreasing the numbers of agents used in the process. While, as the methods to separate the product easily in investigation stage, following methods were already proposed.
1. Solid-phase synthesis characterizing that the series reactions of molecules locating on the surface of solid dispersed in solvent with molecules dissolved in the solvent are carried out on the surface of solid in the state that the solid is dispersed in solvent.
2. Fluorine compativility-two-phases reaction systems characterized that fluorinated alkanes and the ordinary low polar organic solvent are combined.
3. Reaction system which uses a phase-transfer catalyst in double phases consisting of water and organic solvent.
4. Reaction system in the combination of two or more kinds of organic solvents which control the chemical reactivity of polymer or compound whose ligand is polymer and the refining by separation by changing dissolving ability of polymer carrier which is dissolved or dispersed in solvent, by changing the state of phase separation.
In these reaction systems, the method 2, each components consisting of the solvent are compatible by heating. However, the usable solvent is limited to the low polar solvent which has relatively high affinity with fluorinated solvent of low polar. Further, this method has problems, that is, expensive fluorinated solvent is necessary, the substance to be dissolved is necessary to be fluorinated because it is dissolved in fluorinated solvent, and in the case of reaction dissolving an organic or an inorganic salt, there is a difficulty to handle a polor substance such as biomolecule, because high permittivity solvent does not have this characteristic.
Further, the method 3 can be said as the reaction system which combines high permittivity or high polar solvent with low permittivity or low polar solvent. Although these solvents forms two-phases structure according to the difference of the physical property, the solvent which forms reversibly homogeneous compatible mixed solvent by simplified change of outer condition is not obtained yet. Further, the reaction is limited at the interface of separated two layers, and the reactivity can not be said to be high.
As disclosed in the method 4, when polymer is used as a solute or as an agent, the separation of low molecule component and polymer component accompanying to the phase separation of the solvent can be easily controlled. In the meanwhile, in many chemical reactions, the reaction between low molecule components is carried out. However, in the chemical reaction which uses plural numbers of low molecule substances, the separation of the aimed product from not necessary substances by utilizing strictly the difference of solubility between these low molecule substances in actual level was considered to be difficult. The reason why can be illustrated as follows. That is, when two-phase separation state is formed by combining two or more organic solvents, the components in upper layer solvent and in lower layer solvent are not composed by single component but main component solvent of another layer is mixed.
Therefore, the subject of this invention is to construct the reaction system which solve the problem of controlling the reaction and the problem of separation and refining of the reacted product. In earnest study to solve these problems, the inventors of the present invention have found that the specific non polar organic solvent and polar organic solvent have different solubility to the chemical component and can transfer reversibly and easily to two solvent states, that is, the homogeneous compatibilized mixed solvent state and the separated solvent state in which the phase is separated by only changing the temperature condition, further, can separate single or plural low molecule solute components whose physical properties are different spatially and almost completely, still further, the substantial reaction condition is only satisfied in homogeneous compatibilized mixed solvent state, thus dissolved above mentioned problems.
Above mentioned non polar organic solvent and polar organic solvent are respectively single organic solvent composed of one organic solvent or mixed organic solvent which mixes two or more solvents belonging to each organic solvent by adequate mixing ratio.
At the dissolving of said problem, for example, the polar solvent which dissolves ordinary electrolyte does not form the homogeneous compatibilized mixed solvent state with non polar organic solvent by simple condition, and especially it is difficult to make it reversible. However, in the solvent system which is found out by the inventors of the present invention, one solvent can dissolve electrolyte, and the homogeneous compatibilized mixed solvent state dissolving electrolyte—the separable state by dissolving electrolyte only in single organic solvent mainly composed of one organic solvent which is phase separated or mixed organic solvent can be accomplished reversibly only by controlling the temperature. The discovery of this phenomenon is an unexpected one, and said solvent system is extremely useful for the designing and construction of various reaction system in the future, because ionic substance is frequently used in the reaction system and the separation of ionic substance after reaction is difficult. Further, this solvent system can construct the functional system which control not only reaction process but also refining process, compativility—phase separation, for example, the system which flows an electric current at the critical temperature, and is hopeful as the new functional material.
Further, the inventors of the present invention are aimed to use said solvent system practically and have synthesized the compound which is utilized so as the practical use of the solvent system to be possible, for example, have designed the compound having a bonding part of amino acid unit from which the formation of peptide in the method for peptide synthesis is initiated with a residue which make the utilization of the solvent system possible such as the compound represented by following general formula A, and have constructed the reaction system utilizing the solvent system positively.

In general formula A, L1 is hydroxyl group which bonds with amino acid, a single bond which bonds with thiol group, amino group or carbonyl group, an atomic group which bonds with said hydroxyl group, thiol group, amino group or carbonyl group or an atomic group which forms fused aromatic ring of two rings bonding with dotted line, wherein the dotted line is an atomic group which forms said fused aromatic ring by bonding with H or L1, X is O, S, ester group, sulfide group or imino group, R is hydro carbon group of carbon number 10 or more which can contain O, S or N having a possibility to improve the solubility to cycloalkane solvents as a bonding atom, n is a integer from 1 to 5, further in the case when said hydro carbon group of carbon number 10 or more is to improve the solubility to cycloalkane solvents, R possesses a side chain with functional group which bonds with the amino group and/or substituent.
From the technical view point, the residue of the compound represented by general formula A is called as carrier in the present invention.
This peptide synthesis reactions can be applied to the synthesis of oligomers or polymers such as protein, DNA, RNA or polysaccharides.